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Alexithymia is associated with substance abuse and may interfere with successful psychotherapy. Alexithymia’s relation to smoking, nicotine dependence, and smoking cessation therapy is unknown, and potentially overlaps with negative affect. Three studies addressed the relations between alexithymia, negative affect, and smoking. In Study 1, 67 young adult smokers were more depressed than 370 past or never smokers, but no different on the Toronto Alexithymia Scale total or sub-scale scores. In Study 2, negative affect – but not alexithymia – was related to greater nicotine dependence among 99 chronic smokers. In Study 3, alexithymia tended to predict increased patient participation in cognitive-behavioral therapy for smoking; low nicotine dependence – but neither alexithymia nor negative affect – predicted abstinence from smoking at treatment end. Alexithymia appears to be independent of negative affect and unrelated to cigarette smoking or nicotine dependence, suggesting that the affect regulation deficits in alexithymia play a negligible role in nicotine addiction.