Post-sclerotherapy hyperpigmentation is a common adverse effect, particularly when complicated by Nicolau syndrome, a rare injection-related event that can lead to tissue necrosis and persistent pigmentary changes. We report a case of a 40-year-old woman with Fitzpatrick skin type II, who developed longstanding hyperpigmentation in the right popliteal area following polidocanol sclerotherapy. Clinical and dermoscopic examination revealed mixed melanin and hemosiderin deposition. The patient was successfully treated using a quadrant-specific multimodal laser approach combining intense pulsed light (IPL), Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG), and erbium-doped yttrium aluminum garnet (Er:YAG) lasers over two sessions. Notable pigment clearance, full crust exfoliation, and restoration of normal skin tone were achieved without adverse effects. Independent expert evaluation and patient-reported outcomes confirmed the treatment's efficacy and high tolerability.