Twelve soft tissue tumors preoperatively studied with magnetic resonance (MR) imaging contained areas of inhomogeneous intralesional signal intensity. The pathologist's selection of biopsy sites from gross specimens was based on specific MR images selected by a radiologist and depended on close cooperation between the radiologist and pathologist. The histopathology so sampled, further depended on the lesion's size, careful gross specimen orientation, discrete sampling, and a specially developed Grid Analysis technique. Our initial experience indicates that (1) histology may vary within different and often neighboring sites of a single soft tissue lesion; (2) that such variability is common in soft tissue tumors; (3) that histological variability within different sites of a single lesion influences signal heterogeneity; and (4) that although differing MR signal intensities per se are not tissue specific, MR may enhance the histopathological accuracy of pathologists who can be directed to particular gross specimen sites by magnetic resonance images. To our knowledge such a specific, detailed effort has not been made.