Recent findings in understanding the causal role of blood mosaic protein-truncating DNA variants in leukemia prompt questions about generalizability of such observations for other cancer types. We used exome sequencing to compare 22 different cancer phenotypes from TCGA data (~8,000 samples) with more than 6,000 controls using a case-control study design and demonstrate that mosaic protein truncating variants in these genes are also associated with solid-tumor cancers. We analyzed tumor DNA samples from TCGA and observed that the cancer-associated mosaic variants are absent from the tumors. Through analysis of different cancer phenotypes we observe gene-specificity for mosaic mutations. PPM1D in previous reports has been linked to breast and ovarian cancer, which our analysis confirms as a specific gene for ovarian cancer. Additionally, glioblastoma, melanoma and lung cancers show gene specific burden of the mosaic protein truncating mutations. Taken together, these results extend existing observations and link solid-tumor cancers to somatic blood DNA changes.