Small‐cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs. We examined the antimetastatic effects of the humanized anti‐ganglioside GM2 (GM2) antibodies, BIW‐8962 and KM8927, compared with the chimeric antibody KM966, in a SCID mouse model of multiple organ metastases induced by GM2‐expressing SCLC cells. BIW‐8962 and KM8927 induced higher antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity than KM966 against the GM2‐expressing SCLC cell line SBC‐3 in vitro. These humanized antibodies inhibited the production of multiple organ metastases, increased the number of apoptotic cells, and prolonged the survival of the SCID mice. Histological analyses using clinical specimens showed that SCLC cells expressed GM2. These findings suggest that humanized anti‐GM2 antibodies could be therapeutically useful for controlling multiple organ metastases of GM2‐expressing SCLC. (Cancer Sci 2011; 102: 2157–2163)