BACKGROUND Sebaceous carcinoma is a rare malignant tumor of the skin adnexa. While surgical resection is a treatment of choice in localized disease, frequent recurrence and distant metastasis make treatment difficult. Moreover, due to its rarity, optimal systemic treatment has not been determined. CASE REPORT A 59-year-old female presented with disseminated subcutaneous nodules. Past history indicated she received repeated surgery, radiation therapy, and fluorouracil-based systemic chemotherapy for recurrent sebaceous carcinoma. Following a subcutaneous nodule biopsy, histopathologic examination confirmed recurrent metastasis of sebaceous carcinoma. Because there was no established regimen as salvage chemotherapy, we decided to administer paclitaxel plus Adriamycin as a combination regimen after a thorough search of previous reports on PubMed. After the patient received 6 cycles of chemotherapy, all masses dramatically regressed. Unfortunately, several new lesions appeared 3 months after cessation of chemotherapy. Therefore, she was treated with anti-HGF antibody through a clinical trial. After that, she received nivolumab. But treatment with all the new agents did not show any response. Furthermore, her disease progressed rapidly. We re-challenged with the paclitaxel and Adriamycin regimen, 2 cycles of chemotherapy, and the follow-up positron emission tomography - computed tomography revealed marked decrement of multiple metastatic nodules. CONCLUSIONS Although several clinical reports have shown the effectiveness of fluorouracil, especially 5-fluorouracil-based chemotherapy, there has been a paucity of reports on other chemotherapeutic agents. We report a case of metastatic sebaceous carcinoma which showed favorable response to non-fluorouracil-based chemotherapy.