Orchitis of viral or presumed viral etiology is an uncommon cause of testicular pain or enlargement. Rarely orchitis is clinically or radiographically suggestive of neoplasia, resulting in a testicular biopsy or orchiectomy being performed. Between 1978 and 2004, 10 cases submitted in consultation were diagnosed as orchitis at the Massachusetts General Hospital. The patients were from 18 to 37 years of age and presented with testicular enlargement or a mass, pain, or both. Radiographic studies were suspicious for a neoplasm in all 5 cases in which results were available. The patients underwent testicular biopsy (2 cases), orchiectomy (6 cases), biopsy immediately followed by orchiectomy (1 case), or biopsy followed by orchiectomy 3 weeks later (1 case). The cases were submitted with diagnoses that included intratubular seminoma, intratubular germ cell neoplasia, unspecified, Sertoli cell hyperplasia, myeloid sarcoma, and lymphoma. Microscopic examination revealed preservation of the architecture of the testicular parenchyma, typically with hemorrhage and edema, with patchy inflammation in the form of a lymphohistiocytic infiltrate within seminiferous tubules and also between tubules. The intratubular infiltrate usually predominated. Immunohistochemical studies, performed in 7 cases showed a mixture of CD68+ histiocytes and CD3+ T cells, with few B cells (CD20+) and few granulocytes. Follow-up was available in 5 cases; all 5 patients were alive and well 11 months to 10 years after diagnosis. In the rare instance in which a testicular specimen with orchitis is submitted for pathologic evaluation, diagnosis may be difficult. Familiarity with the pathologic changes characteristic of orchitis will help avoid misdiagnosis.