Antiangiogenic agents are an innovative oral chemotherapy prescribed in metastatic renal cancer and gastrointestinal stromal tumors (GIST). These molecules have several side effects. A woman, with moderate hypertension and severe Thevenard's ulceromutilating acropathy, presented renal cancer with lung metastasis. She was treated by antiangiogenic therapy (sunitinib). Under this treatment, she presented some large, extensive, severe and necrotizing ulcerations of both hands and feet, exacerbated with a sepsis. Sunitinib was stopped and antibiotics were combined with surgical trimming leading to clinical remission and complete healing. Sunitinib inhibits both tumor angiogenesis and tumor cell proliferation, but also the preexisting microcirculation. In our case, severe neuropathy caused neurovascular dysregulation which, together with hypertensive microangiopathy, led to a severe hand-foot skin reaction. This microangiopathy worsened under anti-VEGF therapy. The clinical severity was linked to the severity of the neuropathy. To avoid having serious cutaneous consequences, neuropathy and microangiopathy have to be diagnosed before introducing antiangiogenic therapy.