Testicular germ cell tumors are important neoplasms and seminoma accounts for 40 to 50% of these tumors. Little is known concerning the molecular events underlying the development of these malignancies. In the present study we used a modified differential display approach to compare gene expression between seminoma and normal testicular parenchyma, both of which are mixed tissues. We first analyzed mRNA (cDNA) expression by differential display and then directly used differentially expressed cDNAs for the synthesis of radiolabeled riboprobes to attribute differential expression to specific cell types in tissue sections by in situ hybridization. Using this approach along with real-time quantitative reverse transcriptase-polymerase chain reaction analysis we found an overexpression of eukaryotic initiation factor 3 p110 mRNA (EIF3S8) in seminoma cells compared to normal germ cells of testicular tubules. The elF3-p110 subunit may promote seminoma development by generally increasing translation leading to enhanced cellular growth and division rates.