Dexamethasone (Dex), alone or in combination, is commonly used for treating multiple myeloma. Dex as single agent for initial therapy of myeloma results in overall response rates of 50-60%. It is unclear whether steroid responsiveness reflects any biological characteristic that impacts long-term outcome. We studied a cohort of 182 patients with newly diagnosed myeloma seen between March 1998 and June 2007, initially treated with single-agent Dex for at least 4 weeks. The median age at diagnosis was 63 years (range, 39-81) and the median estimated survival was 55 months. At a median duration of therapy of 15 weeks, 91 (50%) patients had a partial response or better, 80 (44%) had less than partial response and the remaining (6%) patients were not evaluable. The median overall survival from diagnosis for the responders was 75 months compared to 71 months for remaining patients, P = 0.6.There was no correlation between baseline disease characteristics and Dex responsiveness. While overall survival was longer for the 130 (70%) patients who proceeded to an autologous stem cell transplant, no correlation was found between survival and Dex responsiveness among either group. Among this cohort of patients with myeloma, failure to respond to single agent steroid did not have an adverse impact on eventual outcome.