Object One of the major difficulties of conducting bone metastasis research is the lack of adequate models for studying the bone–tumor microenvironment. The limitations of current in vivo models include the following: non-human tumor or bone, variable reproducibility, limited supply, and an inability to be easily manipulated. The objective of the present study was to develop a uniform and reproducible model of bone/spine metastasis by utilizing bone derived from human osteoblasts grown subcutaneously in severe combined immunodeficiency (SCID) mice with subsequent introduction of human carcinoma cell lines. Methods Human osteoblasts were serially passed in culture and induced to differentiate into mature osteoblasts. They were subsequently loaded on hydroxyapatite-coated collagen sponges and implanted subcutaneously into the SCID mice. After allowing the bone to mature for 8 weeks, tumor cell suspensions were implanted percutaneously into the bone. The bone–tumor complexes were subsequently harvested, decalcified, and prepared for histological examination. Conclusions The authors have developed a novel, reproducible SCID mouse model of bone/spine metastasis by using bone derived from human osteoblasts and subsequently introduced human tumor lines. They believe this model will be useful for studying the basic biology of bone metastases.