This chapter presents the case scenarios of a 70‐year‐old woman who has an enlarging mass in the right axilla. A carefully placed biopsy with adequate tissue for diagnosis could have allowed this woman a limb‐sparing resection with an excellent chance of local control and probable cure. There are various methods of biopsy that are available to clinicians when a histologic analysis is required for a patient presenting with a soft tissue mass. The three most common options available are incisional biopsies, core needle biopsies, and fine needle aspirations. Biopsies are a critical step in the timely diagnosis and treatment of soft tissue masses. Some debate exists on the safety and outcomes of soft tissue biopsies performed in a nonspecialized community setting compared to those performed by experienced personnel in a specialized sarcoma center. The chapter provides recommendations for implementing evidence‐based practice in the clinical setting.