Mesenchymal neoplasms of the scrotum are extremely rare in the clinical practices, in which lipoma is the most common benign neoplasm of them. Primary scrotal lipoma refers to the lipoma originated from scrotal wall. We reported a rare case of a 47-year-old man who suffered from bilateral giant primary scrotal lipoma along with lipomas in multiple sites of the body. Scrotal ultrasound indicated that huge hypoechogenic masses were observed in the bilateral scrotums. Contrast-enhanced computed tomography (CT) indicated increased fat density in the scrotal areas. Surgical resection was performed on both scrotal neoplasms. Diagnosis of lipoma was confirmed by the pathological examination through the morphological observation as well as the absence of murine double minute2 (MDM2) gene amplification in the fluorescence in situ hybridization (FISH) test. After five months of follow-up, the wound of the patient recovered well and no sign of local recurrence was observed. Based on the literature review, very few cases of primary scrotal lipoma were reported in the scientific literature up to date, and this is the first report of bilateral primary scrotal lipoma along with multiple lipomas of the body. We presented this case as a rare phenomenon. Although primary scrotal lipoma is rare, clinicians should take it into account when encountering similar scrotal lesions and know the methods for diagnosis and how to make differential diagnosis with other diseases, which is associated with the patient's treatment strategy and prognosis. 2021 Translational Andrology and Urology. All rights reserved.