Cyclo-oxygenase-2 has been demonstrated in primary and metastatic melanoma suggesting that it may have a functional role and be a potential therapeutic target. Celecoxib, which was approved by Health Canada for familial adenomatous polyposis coli, was offered to 27 patients with surgically incurable recurrent melanoma, 87 percent of whom had stage M1c disease. In this case series, 6 patients had received prior systemic therapy and one had prior CancerVax. Tumor regressions were seen in 7 patients (2 complete regressions, 2 partial regressions, and 3 mixed stable/partial response). For all patients, median overall survival time from first incurable metastasis was 31.9 months, and median times to progressive disease and death from start of celecoxib were 4.3 months and 10.4 months, respectively. Further clinical evaluation of celecoxib in melanoma is warranted.