Testicular tumors are both increasing in frequency and disproportionately occur in young men; furthermore, different forms of neoplasm require different treatments. These considerations make the accurate diagnosis of testicular tumors especially important. Many of the critical distinctions involve the differentiation of seminoma from one or more potential mimics because seminoma is not only the most common testicular neoplasm but it is also the only malignant testicular tumor that is commonly treated with radiation, which is ineffective in other malignancies of the testis. For the most part, accurate diagnosis can be achieved by careful light microscopic evaluation, although appropriate immunostains can provide diagnostic assistance if doubt persists. This article discusses a number of clinically important differential diagnoses in the testis that are common sources of misinterpretations. These include: seminoma versus embryonal carcinoma, seminoma versus yolk sac tumor, seminoma versus Sertoli cell tumor, seminoma with syncytiotrophoblast cells versus choriocarcinoma, granulomatous seminoma versus granulomatous orchitis, intertubular seminoma versus orchitis, lymphoma versus seminoma or embryonal carcinoma, dermoid cyst versus teratoma, scar versus regressed germ cell tumor, and “anaplastic” spermatocytic seminoma versus usual seminoma or embryonal carcinoma.