Limb-sparing resection and reconstruction has become the treatment of choice in extremity malignancies, as amputation does not provide better long-term survival rates or functional advantages. R0 resection, the removal of the tumor in sano, remains the prerequisite and most important oncologic parameter to avoid local recurrence. Successful treatment requires the combination of surgical eradication and the patient's specific functional and aesthetic rehabilitation. Our clinical rationale resulting from more than 2000 cases will be demonstrated. The problematic aspects of different tumor entities and the locoregional clearance of lymphatic pathways will be discussed. Differential diagnosis and multimodality treatment in high-volume tumor centers is likely to achieve superior oncologic statistics. Long-term survivors after microsurgical reconstructions and possible secondary malignancies will be addressed.