The pathogenesis of benign bone lesions is unclear. One possible cause seems to be an anachronistic behavior of certain cell types (being in the wrong place at the wrong time). Thus, for certain benign chondrogenic tumors such as enchondroma and osteochondroma, spatial and temporal misdirection of proliferating chondrocytes from the growth plate is discussed to result in persistence of cartilage cells in the wrong location. Other explanations include traumatic or hemodynamic causes (e.g. simple bone cyst). Hereditary osteochondromatosis is known to have an autosomal dominant inherited genetic defect. Other syndromes, such as Ollier’s disease (enchondromatosis) and Mafucci’s syndrome are not hereditary but show spontaneous gene mutations.

Rarely, malignant bone tumors can develop on the basis of pre-existing „precursor lesions“. Among these, Paget’s disease, radiation, bone infarcts, chronic osteomyelitis, and some preexisting benign bone tumors represent known precancerous conditions. However, the majority of primary malignant bone tumors arise „de novo“, i.e. for no known reason.

The etiology of most benign and malignant soft tissue tumors is also unknown. In rare cases, genetic influences, environmental factors, radiation, viral infections, and immunodeficiencies have been associated with the development of malignant soft tissue tumors. Furthermore, there are isolated reports of soft tissue sarcomas arising in scar tissue, adjacent to fractures, and near surgical implants. However, the vast majority of soft tissue sarcomas also appear to arise „de novo“, i.e., without any identifiable cause.