Hemangiomas are the most common benign tumor of childhood. Clinical management is limited primarily to observation. Non-surgical treatment modalities have had mixed results and with morbid side effects. Improved understanding of angiogenesis over the last two decades is helping to delineate differences between various vascular tumors. This molecular understanding will be central in helping to properly diagnose and potentially treat these childhood tumors. While a number of downstream effector cytokines have been shown to have altered expression in hemangiomas, a cause for the primary dysregulation within hemangiomas has not yet been clarified. Upstream modulators of angiogenesis are now being defined. Homeobox (Hox) genes are master transcription factors, which have a centrol role during organogenesis, and more recently have been documented to be involved in postnatal tissue remodeling and tumor angiogenesis. We document increased expression of Hox D3 in proliferating hemangiomas and propose a potential role for Hox A3, B3, A5 and D10.