Background: Classic Kaposi's sarcoma (CKS) is distinguished by nodules and clustered papules over the extremities with persistent edema. Aim: This report examine the results of neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser for the treatment of numerous nodular symptomatic nodules in CKS patients' lower extremities that are ineligible for systemic therapy. Methods: Each lesion received two sessions Nd:YAG laser treatment performed at 1-month intervals. Pretreatment and follow-up visit (after 3 months) were accompanied by clinical photographs and improvement was assessed by a skilled medical professional by comparing before- and after-treatment photos as well as by looking at patients directly. Videodermoscopy was performed on all lesions. Results: Just one session with long-pulsed Nd:YAG laser proved to be successful, with the immediate coagulation of the lesions and the disappearance of most of them. Every single lesion healed in two to 4 weeks. Only one lesion, the largest one, presented a water blister after treatment, which resolved within a few days. At 2 months follow up, the patient reported total pain relief and full recovery after the symptomatic nodules vanished. Conclusion: Nd:YAG laser could represent a rapid and advantageous therapeutic approach for both early- and advanced-stage CKS patients.