OBJECTIVE Although core biopsy is the standard for percutaneous bone biopsy in most other organs aspiration biopsy is frequently performed. We prospectively evaluated 138 patients with skeletal lesions, performing both core and aspiration biopsies to determine if these techniques have a complementary role. METHODS Over a 2-year period, 138 consecutive patients underwent skeletal biopsy. In each patient, two or three histologic cores were obtained percutaneously using standard techniques followed by a single aspiration pass with a 22-gauge spinal needle and 20 cc of negative pressure. Histologic and cytologic evaluations of cores and aspirates were interpreted according to usual pathologic and cytologic criteria. Results were classified as matches (positive or negative), mismatches (aspiration or core only positive), mismatches (either aspiration or core more specific), insufficient samples, inaccurate diagnoses, and both false-negative. RESULTS Twenty-eight patients had specific neoplasms diagnosed on both core and aspiration biopsy, and 40 patients were negative on both. The diagnosis was made only by core in 17 and only by aspiration in 11. Core was more specific in 11, and aspiration was more specific in seven. There were three insufficient cores and 18 insufficient aspiration specimens. One false-negative result was seen by both techniques, and the cytology of two aspiration biopsies was misinterpreted. CONCLUSIONS A complementary role exists for aspiration and core skeletal biopsy, and we suggest both should be routinely performed.