Because many skin lesions and disorders can appear similar, primary care clinicians often struggle to diagnose them definitively without histopathologic information obtained from a biopsy. This review article explains how to decide whether a lesion should be biopsied and what type of biopsy technique to use and then outlines the stepwise approach to each of the most common skin biopsy techniques: shave, saucerization, punch, fusiform, and subcutaneous nodule biopsies. Finally, potential pitfalls and complications are discussed so the clinician can avoid those and can provide a cosmetically acceptable result from these common outpatient procedures.