AbstractCapecitabine, the oral prodrug of 5‐fluorouracil, is indicated in people to treat various malignant epithelial cancers. In dogs, capecitabine has not been extensively evaluated. The aim of this retrospective study was to investigate toxicity and preliminary efficacy of single agent capecitabine in dogs with advanced malignant epithelial cancers of any site, for which no effective therapy existed, conventional treatment failed or was declined. Capecitabine was administered orally at 750 mg/m² from day 1 to 14, followed by 1‐week rest period, given as 3‐week cycles. Safety evaluation was performed after 2 cycles, and every 2–3 cycles thereafter. Tumour response was determined every 2–3 cycles. Twenty‐five dogs with hepatocellular carcinoma (n = 6), lung papillary carcinoma (n = 4), anal sac adenocarcinoma (n = 3), colic adenocarcinoma (n = 2), and other individually represented epithelial cancers (n = 10) were included. Dogs received a median of 4 cycles (range, 2–43) for a median of 84 days (range, 42–913). Toxicity occurred in 17 (68.0%) dogs; the most frequent adverse events were gastrointestinal, with the majority being self‐resolving and of mild grade. Of the 22 dogs with macroscopic disease, 3 (13.6%) achieved partial remission, 16 (72.7%) were stable and 3 (13.6%) progressed; overall clinical benefit rate was 86.4%. Median progression‐free interval was 93 days (95% CI 42–154; range, 1–521) and median tumour‐specific survival was 273 days (95% CI 116–482; range 45–913). These findings suggest that capecitabine is an attractive option for the treatment of several types of carcinomas in dogs. Prospective studies are warranted to optimize the scheduling of capecitabine and confirm its efficacy.