Lymphatic endothelial cell (LEC) proliferation or differentiation in lymphangioma was investigated by immnohistochemical study with D2-40, MIB1, and Prox1. Clinical types of 14 lymphangioma cases were classified into two groups, i.e. macrocystic type (Ma) and microcystic type (Mi); Ma was classified into two subgroups of large cysts (MLC) and small cysts (MSC). In Mi, the number of LECs stained with D2-40 was significantly higher than those of MLC and MSC. The MIB1 index that indicats proliferation activity showed a significantly lower score in MLC than in Mi and MSC. The Prox1 index score of MSC was significantly higher than in the other 2 groups. This study suggests that proliferating activity of LECs in Ma and MSC are higher than that of MLC, and differentiation to LEC in MSC might be higher than those of MLC and Mi. Prox1 is likely to participate more in local development of lymphatic vessels after surgical and/or radiological intervention in MSC than in Mi.