The purpose of the study was to evaluate the feasibility of image-guided percutaneous needle biopsy to enable specific subtype classification of liposarcoma in patients with previously diagnosed disease and compare the yield of fine and large needle techniques for each subtype. We reviewed the medical records and pathology reports of 69 fine (20 g) needle and large (15, 16 g) needle biopsies performed in 44 patients enrolled in a clinical trial evaluating the effect of a novel therapy for advanced liposarcoma in the abdomen and pelvis. Cytopathologists and surgical pathologists identified features that enabled them to classify the tumor into one of four subtypes: well differentiated, myxoid/round cell, pleomorphic and dedifferentiated. The pre-study open surgical biopsy was used as the standard for comparison. The diagnostic yield (proportion of biopsies with correct subtype diagnosis) of percutaneous biopsy for identifying all subtypes of liposarcoma was 81% (64% for fine needles and 73% for large needles alone). There was a significant association between pathologic subtype and the probability of a correct diagnosis (P=0.05). Accurate diagnostic subset classification of liposarcoma by percutaneous biopsy is feasible, although both fine and large needles should be used. Although these data cannot be extrapolated to primary diagnosis of liposarcoma, they are important for screening and subtyping of possible recurrence.