BACKGROUND: Giant congenital melanocytic nevus (GCMN) is a rare disease, for which complete surgical resection is recommended. However, the size of the lesions presents problems for the management of the condition. The most popular approach is to use a tissue expander; however, single-stage expansion in reconstructive surgery for GCMN cannot always address the entire defect. Few reports have compared tissue expansion techniques. The present study compared single and serial expansion to analyze the risk factors for complications and the surgical outcomes of the two techniques. METHODS: We retrospectively reviewed the medical charts of patients who underwent tissue expander reconstruction between March 2011 and July 2019. Serial expansion was indicated in cases of anatomically obvious defects after the first expansion, limited skin expansion with two more expander insertions, or capsular contracture after removal of the first expander. RESULTS: Fifty-five patients (88 cases) were analyzed, of whom 31 underwent serial expansion. The number of expanders inserted was higher in the serial-expansion group (P<0.001). The back and lower extremities were the most common locations for single and serial expansion, respectively (P=0.043). Multivariate analysis showed that sex (odds ratio [OR], 0.257; P=0.015), expander size (OR, 1.016; P=0.015), and inflation volume (OR, 0.987; P=0.015) were risk factors for complications. CONCLUSIONS: Serial expansion is a good option for GCMN management. We demonstrated that large-sized expanders and large inflation volumes can lead to complications, and therefore require risk-reducing strategies. Nonetheless, serial expansion with proper management is appropriate for certain patients and can provide aesthetically satisfactory outcomes.