Many people die from lung and breast cancer. Consequently, both physicians and researchers strive to provide reliable monitoring for disease, diagnosis and prognosis as well as resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients to examine the importance and spectrum of recurrent somatic cancer mutations. Most patients visited the clinic with a diagnosis of advanced resistant cancer. The patients underwent a comprehensive liquid biopsy panel. Patients were divided into four groups based on cancer type as follows: Lung (n=379, 79.9%), breast (n=72, 15.2%), gastrointestinal (n=11, 2.3%) and other (n=12, 2.5%). Tier I-II-III classified variants were included in the study. The mean age was 60 years, with a range of 20-86 years. There were notably more male (n=272, 57.4%) than female patients (n=202, 42.6%). The most commonly mutated genes were TP53, EGFR, PIK3CA, RET, PTEN, MET, ATM and KRAS. The most common mutations were 'PIK3CA, c.3140A>G, p.His1047Arg', 'RET, c.2324delinsGAC, p.Glu775Glyfs*6', 'TP53, c.217G>C, p.Val73Leu', 'EGFR, c.2155G>A, p.Gly719Ser', 'PIK3CA, c.1624G>A, p.Glu542Lys', 'PTEN, c.397G>A, p.Val133Ile' and 'EGFR, c.2235_2249del, p.Glu746_Ala750del'. The PIK3CA, PTEN and RET variants showed a higher incidence in the breast and lung groups compared with other groups. To the best of our knowledge, the present study is the first to concentrate on PIK3CA, PTEN and RET mutations in the context of breast and lung adenocarcinoma and to evaluate both genetic variability and the effect of treatment. The present results showed that patients with solid tumors, particularly lung and breast cancer, may benefit from PIK3CA, PTEN and RET sequencing to assess clinical characteristics and prognosis. Discoveries regarding the gene structure and mechanisms of PIK3CA, PTEN and RET may inform more clinically meaningful therapeutic approaches for patients with cancer and serve an essential role in improving individual risk prediction, therapy and prognosis.