Spermatocytic seminoma (SS) is an unusual germ cell tumor that behaves in an indolent fashion. Because orchiectomy alone in adequate treatment, it is important to distinguish SS from classic seminoma and other germ cell tumors. Light microscopic distinction usually is possible; however, occasional cases of SS exhibit atypical features, including the presence of a lymphoid infiltrate or microcystic change, which simulate classic seminoma and yolk sac tumor, respectively. Immunohistochemistry might aid in this differential diagnosis, but the immunohistochemical profile of SS is not well reported in the literature. We examined seven SS cases (six men and one non-human primate) with a panel of 14 antibodies directed against placental-like alkaline phosphatase (PLAP), keratins (CAM 5.2, AE1/AE3), vimentin, human chorionic gonadotropin, alpha-fetoprotein, muscle-specific actin, carcinoembryonic antigen, S-100 protein, epithelial membrane antigen, desmin, leukocyte-common antigen, neuron-specific enolase, and human placental lactogen. A previously unreported finding was the presence of focal cytoplasmic staining for low molecular weight cytokeratin (CAM 5.2) in three cases. All other antibodies produced essentially negative results, including anti-PLAP. The PLAP and neuron-specific enolase negativity of SS are in contrast to the positivity of classic seminoma for these markers. A simplified panel of antibodies is recommended to assist in the differentiation of SS from other forms of germ cell neoplasia.