Germline mutations are congenital genetic mutations in germ cells that originate from sperm or ovum and are generally incorporated into every cell of the offspring's body. Somatic mutations are acquired genetic mutations that form under the influence of environmental factors during embryo formation and epigenetic development. Generally, only a portion of the cells in the human body have the same somatic mutations. Clinical detection of germline mutations is intended to determine inherited malignancies and identify high‑risk families, and detection of somatic mutation is proposed to find targeted drugs, monitor tumor loading for guided therapy, and evaluate prognosis. Large‑scale population cohort studies have shown that germline mutations are closely related to the occurrence, development, and prognosis of diseases. Patients with cancer‑predisposition germline mutations can be used as sentinels in high‑risk families. Traditional histopathology is no longer enough to identify types of cancers. Even within a particular type of tumor, there is great heterogeneity between internal molecules. The Pan‑Cancer Research Program as well as other projects seek to use large quantities of data from different types of tumor research databases to carry out integrated analysis in order to establish potential non‑tumor‑specific tumor markers and targets by increasing the sample size to identify more molecular mechanisms. This review intends to summarize some of the relevant mechanisms underlying germline mutations in blood disorders.