We present a case report of a patient with metastatic small cell neuroendocrine carcinoma of the breast (SCNCB), a high-grade neuroendocrine triple-negative breast cancer, who achieved a complete response after two cycles of sacituzumab govitecan-hziy (SG) (Trodelvy) as third-line systemic therapy. She originally presented with estrogen receptor-positive disease, and we were able to clearly demonstrate transformation into triple-negative SCNCB via serial tissue biopsies. This is the first reported case of SG for SCNCB, and it shows an outstanding response in a patient who had undergone prior systemic therapies. Clinical trials are needed to address the potential role of TROP2 inhibition and the use of SG as a therapy for SCNCB.