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病因学与遗传学、分子生物学的迅速发展和对肿瘤发生、发展易感性的遗传改变的关注在软组织肉瘤尤为显著。家族性疾病如神经纤维瘤病、成视网膜细胞瘤和多发性息肉病与软组织肉瘤相关。已指出Li-Fraumeni综合症和成视网膜细胞瘤的基因位点是p53。此基因异常对诊断明显相关,但尚未以之用于临床。在病因学上软组织肉瘤与既往放射治疗、化疗和淋巴水肿的联系已经描述。与化学物质、特别是二哦英类（dioxins）接触的危险已倍受关注。
The focus on etiology and genetics, the rapid development of molecular biology, and the genetic changes in susceptibility to tumorigenesis and development are particularly evident in soft tissue sarcomas. Familial diseases such as neurofibromatosis, retinoblastoma, and polyposis are associated with soft tissue sarcomas. It has been pointed out that the gene site of Li-Fraumeni syndrome and retinoblastoma is p53. This gene abnormality is obviously related to diagnosis, but it has not yet been used in clinical practice. The association of soft tissue sarcoma with previous radiotherapy, chemotherapy, and lymphedema has been described in etiology. The dangers of exposure to chemicals, particularly dioxins, have received much attention.