Inclusion Criteria: - History of primary mucosal or acral/lentiginous melanoma - Histologically documented stage III unresectable or IV metastatic melanoma - ECOG Performance Status 0,1 or 2 - Estimated life expectancy of 6 months or greater - 18 years of age or older - Lab values as outlined in protocol - Tumor blocks or slides must be available of either primary or metastatic tumor site for c-kit mutation testing - Negative pregnancy test within 48 hours of starting treatment - At least one measurable site of disease as defined by at least 1cm in greatest dimension Exclusion Criteria: - Severe and/or uncontrolled medical disease - Pregnant or nursing mothers - Known brain metastasis. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan - Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or cervical carcinoma in situ - Grade III/IV cardiac problems as defined by the New York Heart Association Criteria - Ongoing cardiac dysrhythmias of grade 2 or greater, atrial fibrillation, QTc interval >450msec for males of >470 msec for females - Hypertension that cannot be controlled by medication - Any of the following within 12 months prior to starting treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism - NCI CTCAE version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment - Concurrent treatment with warfarin - Prior treatment with SU011248 or any other antiangiogenic agent - No H2 blockers or proton pump inhibitors - Known chronic liver disease - Known HIV infection - Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 4 weeks prior to study entry - Major surgery within 4 weeks prior to study entry - Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication