Lineages of Borrelia burgdorferi, the bacterium that causes Lyme disease, can be characterized by distinct alleles at the outer surface protein C (ospC) locus. The lineages marked by ospC genotypes have been shown to be differentially invasive in different species of mammals, including humans; genotypes A, B, I, and K effectively disseminate to human blood and cerebrospinal fluid. In this report, we extend the sample of genotypes isolated from human blood to include genotypes N, H, C, M, and D, and rank each by their probability of disseminating from ticks to the blood of humans. Our results demonstrate that only some genotypes of B. burgdorferi present in ticks have a high propensity to disseminate in humans.