While acral erythema associated with conventional cytotoxic chemotherapy is characterized by symmetric, well demarcated edema and erythema of the palms and soles that can blister and ulcerate, hand-foot skin reactions seen in patients treated with agents targeting VEGFR, manifest with localized painful blister or hyperkeratosis patches in areas of friction or repetitive trauma (heel, lateral aspects of the soles, lateral sides of the fingers and the periungual regions, web spaces, dorsal surfaces of the hands and feet), that start within the first two to four weeks of therapy. This evidence concerns the gene KDR and Erythema.