BACKGROUND Simple (unicameral) bone cysts (SBCs) are benign, fluid-filled bone lesions that are typically solitary and can be unicameral (single chamber) or septated. Most commonly affecting the long bones of children and adolescents, SBCs can be asymptomatic or associated with pain or fractures. Multifocal SBCs, featuring multiple cysts across different bones, are exceptionally rare and pose unique diagnostic and therapeutic challenges. Here, we report an exceptional case of a 20-year-old woman with multifocal SBCs affecting 9 known anatomical sites and discuss the unique diagnostic and therapeutic challenges. CASE REPORT A 20-year-old woman presented with right proximal tibia pain after a fall. Radiographs and MRI revealed radiolucent lesions in the proximal tibia, distal tibia, and fibula, with additional lesions identified on whole-body scintigraphy in the left proximal and distal tibia, left proximal humerus, and pelvis. Initial biopsy was suggestive of SBCs but inconclusive, and surgical biopsy was required for definitive diagnosis. Histologic evaluation confirmed SBCs, demonstrating cyst walls, cholesterol clefts, and fibrin-like deposits. Treatment included curettage, local adjuvant therapy with argon beam and doxycycline, bone grafting, and doxycycline sclerotherapy for pelvic and distal extremity lesions. At 17 months after treatment, the patient remained asymptomatic, with imaging showing sclerosis and near-complete resolution of the lesions. CONCLUSIONS This report presented a rare case of a young woman with multiple SBCs across 9 anatomical sites. Overall, the management of multifocal SBCs requires a multidisciplinary approach, involving orthopedic surgeons, radiologists, and pathologists for optimal outcomes.