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Regarding inherited cancer predisposition, single gene carriers of pathogenic variants (PVs) have been extensively reported on in the literature, whereas the oligogenic coinheritance of heterozygous PVs in cancer-related genes is a poorly studied event. Currently, due to the increased number of cancer survivors, the probability of patients presenting with multiple primary cancers (MPCs) is higher. The present study included patients with MPCs aged ≤45 years without known PVs in common cancer predisposition genes. This study used whole exome sequencing (WES) of germline and tumoral DNA, chromosomal microarray analysis (CMA) of germline DNA (patients 1–7, 9 and 10), and a karyotype test of patient 8 to detect variants associated with the disease. The 10 patients included in the study presented a mean of 3 cancers per patient. CMA showed two microduplications and one microdeletion, while WES of the germline DNA identified 1–3 single nucleotide variants of potential interest to the disease in each patient and two additional copy number variants. Most of the identified variants were classified as variants of uncertain significance. The mapping of the germline variants into their pathways showed a possible additive effect of these as the cause of the cancer. A total of 12 somatic samples from 5 patients were available for sequencing. All of the germline variants were also present in the somatic samples, while no second hits were identified in the same genes. The sequencing of patients with early cancers, family history and multiple tumors is already a standard of care. However, growing evidence has suggested that the assessment of patients should not stop at the identification of one PV in a cancer predisposition gene. [ABSTRACT FROM AUTHOR]