Vitiligo is a difficult-to-control disease with a devastating impact in the lives of many patients. An association has been shown between the Koebner phenomenon and the occurrence of skin depigmentation in vitiligo. However, the medical literature contains very little information regarding the relationship between varicose veins, a common comorbidity for many patients, and vitiligo skin lesions. We present two cases of generalized vitiligo in which patients experienced delayed or absent repigmentation exclusively over varicose veins after narrowband ultraviolet B therapy, despite repigmentation over the rest of the body. In one case, repigmentation occurred after varicose vein treatment. These patients highlight potential and previously unexplored interactions between varicose veins and response to vitiligo phototherapy. The impact of varicose veins on vitiligo treatment may inform future research ideas into the pathogenesis of this skin disease. Furthermore, these cases suggest a possible mechanism of improving local treatment response in vitiligo by addressing underlying varicose veins.