Myxoid tumors of soft tissues constitute a histogenetically heterogeneous group of lesions, both benign and malignant, that show an overproduction of mucopolysaccharide substances. A correlative fine needle aspiration (FNA) cytologic and histologic study was performed on 16 such cases (3 intramuscular myxomas, 2 lipoblastomas, 6 myxoid liposarcomas, 4 myxoid malignant fibrous histocytomas [MFHs] and 1 extraskeletal myxoid chondrosarcoma), with electron microscopic examination of the aspirate in 4 cases. FNA of all tumors produced a gelatinous material. Smears from all but one of the tumors had a granular myxoid background substance that stained blue to blue-red with the Diff-Quik stain; the exception was the extraskeletal myxoid chondrosarcoma, whose smears stained intensely blue-red to red. On light microscopy, only lipomatous tumors had distinctive cells with diagnostic value: the lipoblasts. Although the arrangement of lipoblasts in lipoblastomas differed somewhat from that found in myxoid liposarcomas, clinical data were important for making a definitive diagnosis. Intramuscular myxomas generally showed a low cellularity composed of fibroblastlike cells with no cytologic atypia. Myxoid MFHs were composed of fibroblastlike cells and macrophagelike cells; the elongated cells with slight-to-moderate nuclear atypia predominated in tumors of low-grade malignancy, while polygonal or round cells with one or more nuclei and marked nuclear atypia predominated in high-grade tumors. Although extraskeletal myxoid chondrosarcoma was mainly differentiated from low-grade myxoid MFH by its metachromatic matrix, ultrastructural studies showed the distinctive distended cisternae with microtubular aggregates in the extraskeletal myxoid chondrosarcoma, thus contributing to the definitive diagnosis.