Ferrari produced four new cars for this years race, the 340 America. Three were Touring barchettas for Ascari, Serafiini and Vittorio Marzotto while the fourth was a Vignale sports tourer for Villoresi. Gigi as he was popularly known had requested a roof over his head so that he would, in his own words not have to sit there for 13 consecutive hours "in a bordello of noise. It had taken him a long time to gain Ferrari's acquiescence due to the old man's belief that you could only win the Mille Miglia in an open car.

Last years winner, Giannino Marzotto was not shy about complaining to Ferrari about the heaviness and poor aerodynamics of the available cars. Ferrari responded as is his manner: "Why build new cars? To beat my own which are already winning everything?". Unconvinced the young Marzotto decided that for 1951 he would improve upon last year's Ferrari with an all-new design of his own based on the Ferrari 212 chassis and running gear. In those days before the widespread use of wind tunnels in auto racing, builders based their designs on what Marzotto called “optical intuition”. Italy of course is renowned for it’s coach builders and for his new car he turned to Sergio Reggiani & Paolo Fontana of Padua. A low slung body with a rounded shape similar to that of an egg or Uovo in Italian was decided upon. Ferrari though had one last trick to play by refusing to send Marzotto the special lower, wider radiator that he had requested necessitating a front end that was higher and less profiled than what had been envisioned by its designer. This caused the front end to get very light at speed.

The race route was again changed. The Brescia/Rome route was much the same as in 1950 but the route from Rome to Florence this time passed through Viterbo and Siena. To attract more entries, there were no less than eleven classes. Some of these were introduced in the hope of eliminating, as far as possible, time wasting technicalities and after race checks. The first cars were flagged off at 9 p.m. on Saturday, and it wasn't until 4:30 a.m. that the fastest of the entries were away. If anything the weather was worse than the year before and to the surprise of many it was Marzotto's private 212 Ferrari that streaked into the lead.

Ascari's Ferrari was involved in a wreck only 16 miles outside of Brescia when he was startled by headlights coming from a side road and left the highway and plowed into a group of spectators. Sadly one of those hit, a prominent local doctor would later succumb to his injuries. As is obligatory in Italy, manslaughter charges were brought against the driver. It would take three years for the case to be settled and for the driver to be cleared of personal responsibility. In the meantime Ascari resolved not to race in the Mille Miglia.

Into Ravenna Marzotto held a five-minute lead over the much larger Villoresi, the power of the larger works cars proving diabolical in the current conditions and Marzotto seemed to have the perfect car for the conditions but alas the little car that could, wouldn't when it was forced to retire with what was thought to be a broken axle. Arriving at the outskirts of Senigallia he had heard a loud drumming noise coming from the rear. Fearing the possibility of a frozen differential tossing his car into the Italian countryside and himself into immortality he stopped a couple of time to investigate. Checking the tires with his hands in the off possibility that this may be the source of the noise he could feel nothing. Reluctantly he decided to withdraw from the race which was won by Villoresi in one of the 4.1s. Later Marzotto would joke that he only withdrew at that point because Senigallia was famous for its fish broth and fried scampi.

Later while Marzotto was having the car serviced at the factory it was found that the problem involving his car was only with one of the tires:

Ferrari patiently listened to my remonstrations until someone told us that the truck with the Uovo had arrived. We accompanied Ferrari to the workshop and I nearly dropped when I saw that the offside tire - the one that I checked personally - sported an enormous rubber blister on its inner wall.

I understood immediately that my fingertips had not reached the point where the thread has come away from the canvas as a result of the high speeds. I could have changed the tire and set off still in the lead in exchange of no more than a few minutes. Ferrari said nothing, but as soon as we got back to his office he picked up a cylinder barrel and threw it at me. I ducked to avoid the missile and exited with a cheery smile: he had risked losing the race, I had lost it.