This paper presents the case of an 85-year-old male affected by classic Kaposi's sarcoma (CKS) since 1994. The disease was widespread over much of the skin surface. Since 1995 the patient had undergone several chemotherapy treatments with good, but not lasting results. Due to a worsening in the pathology, in October 2005 the patient was prescribed a further cycle of vinorelbine. Twenty-four hours after the first infusion, followed by isotonic sodium chloride solution vein wash, a supra-venous serpentine erythematous lesion appeared directly above infusion site. The lesion extended centripetally from the injection point and involved the whole supra-venous area. Over the following days, a gradual variation in lesion colour, from erythematous to hyperpigmented, was observed. Given this clinical and histological picture, the diagnosis of persistent serpentine supra-venous hyperpigmented eruption (PSSHE) was made. Draft of a rare secondary effect whose pathogenesis still remain to explain. The literature holds reports of another skin manifestation with similar supra-venous characteristics: persistent supra-venous erythematous eruption (PSSE), clinical entity that enters in differential diagnosis with the PSSHE. Many of the drugs used in chemotherapy have been indicated as responsible for these peculiar side-effects. To the authors' knowledge, the literature reports only one PHSSE case induced by i.v. vinorelbine infusion.