Renal angiomyolipomas (AMLs) are benign tumors common in tuberous sclerosis complex (TSC), an autosomal dominant disorder (1 in 6,000) caused by TSC1/TSC2 mutations, with AMLs in up to 80% of cases versus 0.3–3% sporadically. Giant AMLs (>4 cm) risk hemorrhage, while TSC-related renal cell carcinoma (RCC) occurs in 2–4% of patients. This case report details a rare TSC presentation with bilateral renal pathology—a right giant AML and left RCC—complicated by situs inversus totalis, highlighting tailored diagnostic and therapeutic strategies.

A 70-year-old female with TSC, diagnosed via cutaneous signs (angiofibromas, adenoma sebaceum), presented with acute bilateral flank pain and hematuria. Imaging (ultrasound, CECT abdomen, CT thorax, MRI brain) revealed a right giant AML (14.2 cm) with pseudoaneurysm, a left complex renal mass (12.9 cm), situs inversus, and TSC features (lung cysts, brain tubers). Transarterial embolization (TAE) with coils addressed the AML’s hemorrhage, followed by left partial nephrectomy for the suspected RCC. Genetic screening confirmed TSC2 mutation. A multidisciplinary team (radiology, urology, genetics) guided management.

TAE successfully controlled hemorrhage from the right AML, preventing nephrectomy. Histopathological analysis of the left renal mass confirmed two distinct tumors: a classic AML and RCC (pT2bN1). Postoperative recovery was uneventful, with stable renal function and no immediate complications.

This case underscores the importance of genetic evaluation, advanced imaging, and a multidisciplinary approach in TSC-associated renal pathology. TAE effectively managed AML-related hemorrhage, while nephrectomy addressed RCC. The presence of situs inversus totalis emphasizes the need for individualized surgical planning to optimize patient outcomes.