Malignant acanthosis nigricans is a rare paraneoplastic syndrome, usually associated with a gastric adenocarcinoma and less frequently with other neoplasms. In general, its appearance indicates a poor prognosis with a survival of < 2 years. We describe the case of a 40-year-old patient who presented with generalized cutaneous thickening that had a velvety appearance, was rapidly progressing, and involved right axillary adenopathy. Skin and nipple biopsy yielded results consistent with acanthosis nigricans, and palpable adenopathy biopsy results were compatible with mammary adenocarcinoma (human epidermal growth factor receptor 2 positive and estrogen and progesterone receptor negative) without a detectable primary tumor. This case of malignant acanthosis nigricans is presented because of the importance of its early recognition as a paraneoplastic syndrome and its relation with mammary adenocarcinoma, an association infrequently reported in the literature.