The number was right in the middle of those assigned to primary East-West roads by the US Department of Agriculture, Bureau of Public Roads in 1925 and that meant that the route it identified would be right in the middle of the country. The original Route 50 was to connect Annapolis, Maryland with Wadsworth, Nevada. By 1927, additional routings brought the western end to Sacramento, California. There have been plenty of changes over the years but the route remains intact and today runs more than 3000 miles from Ocean City, Maryland to West Sacramento, California.
It was William Least Heat-Moon's description in PrairyErth that first turned me on to Route 50 though it seems a natural target. He compares it to 40 and 66 and points out that it includes the Oregon, Santa Fe, and California trails. Part of the Lincoln Highway is in there along with the Overland-Butterfield Stage and Pony Express routes. Heat-Moon writes that he recommended driving its length to someone asking how to "see the full dimension of the country" but he doesn't tell us if the person receiving that advice followed it. I know that I intend to.
More recently, Wulf Berg rekindled my interest when I found his web site promoting the highway and acquired the book documenting his own Atlantic to Pacific drive. In addition to being an interesting read, I expect that book, US 50, Coast to Coast, to be a great help when it comes time to experience Route 50 for myself.