The patellar tendon is the most commonly used graft source in reconstruction of the anterior cruciate ligament. The performance of a patellar tendon graft in such a reconstruction is largely related to the structural and functional differences between patellar tendons and anterior cruciate ligaments. From a genetic point of view, the structural and functional differences are ultimately decided by the differential patterns of gene expression between the two tissues. In the present study, the genetic differences between normal patellar tendons and normal anterior cruciate ligaments were explored by screening a large number of mRNA species to detect the species unique to each tissue. Of the approximately 1,000 mRNAs screened, 20 differentially expressed mRNA species were detected. Eight were unique to patellar tendons, and 12 were unique to anterior cruciate ligaments. Of these 20 unique mRNA species, 12 did not match any of the known sequences in gene databases and were probably novel genes. Transcriptional control is a major step in the genetic pathway; therefore, the variations found between patellar tendons and anterior cruciate ligaments at this level of gene expression indicate that the differences between the two tissues are likely more extensive than previously thought. These differences probably influence the survival of patellar tendon autografts and should be explored further.