Modern cross-sectional imaging methods of computed tomography, sonography and lately MRI have contributed greatly to non-invasive studies of different parenchymal organs and permit the evaluation of pathological changes in different areas of the body. Although these techniques have reached a very high level of refinement, it is often not possible to define whether a focal lesion is benign or malignant. Ultrasound-guided fine-needle aspiration biopsy (FNA) or core-needle biopsy (including high-speed- and vacuum-assisted techniques) are essential to find out the character of the disease in these cases. Experience of more than 10,000 interventions of different organs are presented. Technique, results, problems, as well as risks are discussed. Moreover, it is shown how the results of percutaneous biopsies often change the treatment of a patient. This is especially of interest in those suffering from lymphomas, pancreatic carcinomas, and breast cancers, as well as relapsing tumors.