Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. In NPC, accumulation of cholesterol in tissues could be seen not only in reticuloendothelial and nervous systems, but also in all systems. Our case is important for it being the first case of NPC with submandibular lymphadenopathy characterized with NPC cell infiltration.