HIV infection is associated with a generally increased tumor risk. In the genital region, HPV-associated carcinomas occur frequently. So far, germ cell tumors with somatic malignancy in the form of a rhabdomyosarcoma have been hardly described in HIV infection. We report about a 47-year-old patient with HIV infection and severe psoriasis vulgaris who underwent therapy with adalimumab and developed a huge testicular non-seminomatous germ cell tumor with mature teratoma, yolk sac tumor and somatic malignancy in form of a high grade rhabdomyosarcoma in the area of the right testicle. Upon determination of the tumor, therapy with adalimumab was stopped and the rhabdomyosarcoma was resected. 4 months after ablatio testis, there was a pronounced local recurrence with suspicion of a regional soft tissue metastasis and iliac lymph node metastases on both sides. A further resection was made and adjuvant chemotherapy with epirubicin/ifosfamide was started. An influence of the TNF-alpha-blocker adalimumab cannot be excluded. In HIV infection and simultaneous therapy with TNF-alpha-blockers an increased risk of tumors should be considered.