The histologic, and even the cytologic, diagnosis is straightforward but the problem is capturing the tumor cells which often lie deep within the lesion, surrounded by a protective shell of reactive new bone. If the tumor is extremely osteolytic, you may be able to get a sample with ordinary fine needle aspiration or surgical incisional biopsy, but those examples are infrequent. The biopsy instrument of choice is a bone core biopsy (Jamshidi needle is a common type). Ideally, you should measure the radiograph to predetermine how deeply you have to go in order to capture the osteolytic center of the lesion, which is where the diagnostic cells are going to be.