The aim of this study was to determine cancer susceptibility syndromes (CSSs) in children with lymphoma and solid tumors and to evaluate their effects on overall survival rates. Between 2006 and 2019, the oncologic charts of 672 patients who were followed-up with a diagnosis of lymphoma and solid tumor in our clinic were retrospectively reviewed. CSSs were detected in 42 children (6.25%). The most common CSS was DNA damage repair defects/genetic instability (in 18 of 42 patients with CSSs, 42.8%). In the patients with CSSs, 48 different cancers developed. The most common types of cancer were lymphoma (n: 10, 21%) and high-grade glial tumor (n: 9, 19%). The lymphoma subgroups were very rare childhood lymphomas, such as gray zone lymphoma and marginal zone lymphoma. The overall survival rates for patients with DNA damage repair defects/genetic instability; with CSSs other than DNA damage repair defects/patients with genetic instability syndrome; and without any CSS, were 9.7%, 65.1%, and 68.7%, respectively. The overall survival rate for patients with DNA damage repair defects/patients with genetic instability syndrome was lower than both patients with CSSs other than DNA damage repair defects/genetic instability syndrome (P=0.002) and those without any CSS (P<0.0001). CSSs should be kept in mind in children with cafe au lait spots; syndromic features; a family history of cancer, especially in siblings; and rare childhood cancers.