The purpose of this study was to determine the prevalence, extension and signal characteristics of fluid-fluid levels in a large series of 700 bone and 700 soft tissue tumors. Out of a multi-institutional database, MRI of 700 consecutive patients with a bone tumor and MRI of 700 consecutive patients with a soft tissue neoplasm were retrospectively reviewed for the presence of fluid-fluid levels. Extension (single, multiple and proportion of the lesion occupied by fluid-fluid levels) and signal characteristics on magnetic resonance imaging of fluid-fluid levels were determined. In all patients, pathologic correlation was available. Of 700 patients with a bone tumor, 19 (10 male and 9 female; mean age, 29 years) presented with a fluid-fluid level (prevalence 2.7%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included aneurysmal bone cyst (ten cases), fibrous dysplasia (two cases), osteoblastoma (one case), simple bone cyst (one case), telangiectatic osteosarcoma (one case), "brown tumor" (one case), chondroblastoma (one case) and giant cell tumor (two cases). Of 700 patients with a soft tissue tumor, 20 (9 males and 11 females; mean age, 34 years) presented with a fluid-fluid level (prevalence 2.9%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included cavernous hemangioma (12 cases), synovial sarcoma (3 cases), angiosarcoma (1 case), aneurysmal bone cyst of soft tissue (1 case), myxofibrosarcoma (1 case) and high-grade sarcoma "not otherwise specified" (2 cases). In our series, the largest reported in the literature to the best of our knowledge, the presence of fluid-fluid levels is a rare finding with a prevalence of 2.7 and 2.9% in bone and soft tissue tumors, respectively. Fluid-fluid levels remain a non-specific finding and can occur in a wide range of bone and soft tissue tumors, both benign and malignant. Therefore, they cannot be considered diagnostic of any particular type of tumor, and the diagnosis should be made on the basis of other radiological and clinical findings.