Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity to metastasize (> 30%). Distant metastatic MCC is often treated using chemotherapy but its efficacy is unclear because the existing literature: 1) intermingles adjuvant and therapeutic chemotherapy cases and, 2) often includes combined chemo-radiation. Methods: To assess the efficacy of chemotherapy on MCC we performed a retrospective analysis of 62 patients in our cohort with distant MCC metastases evaluable for response to chemotherapy alone.Tumor responses were characterized as complete remission (CR), partial remission (PR), stable disease (SD) or progressive disease (PD) per RECIST. Overall survival (OS), durability of response and progression-free survival (PFS) were also analyzed. Results: Median age of this cohort was 68 years (range: 47 – 96). Median OS from the start of chemotherapy was 9.5 months. Platinum plus etoposide was the most common first line regimen administered to 69% of the patients. Objective response rate (ORR) with front-line chemotherapy was 54% (34/62) with CR in 15% (9/62) of the patients. 7 of 9 patients with CR eventually progressed. The median progression free survival (PFS) for all patients from start of chemotherapy was 93.5 days with 90% of patients progressing by 290 days. Among responders (CR + PR), median PFS was 161 days, median durability of response was 103 days (range: 12 – 522) and 90% progressed in this subgroup by 428 days. Among 30 patients who received a second line chemotherapy regimen, the ORR was 23% (7/30 with 1 CR, 6 PR). Median PFS from start of second line chemotherapy (n=30) was 61 days (range: 11 – 364). Topotecan was the most commonly used second-line regimen (23%). Conclusions: The results of our study suggest that responses to cytotoxic chemotherapy for MCC are frequent but of limited durability. While subject to selection bias in a retrospective study, these data may be useful as a basis for comparison as the “control arm” for trials of new therapeutic modalities in this rare malignancy lacking data from prospective trials.