Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation abundance between the genome and transcriptome, but there is not yet a systematic understanding of AI. In this study, we performed large-scale DNA and RNA AI analyses of >100,000 somatic mutations in >2,000 cancer specimens across five tumor types using the exome and transcriptome sequencing data of the Cancer Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift indels revealed that nonsense-mediated decay is typical in cancer genomes, and we identified the relationship between the extent of AI and the location of mutations in addition to the well-recognized 50-nt rules. Second, the AI with splice site mutations may reflect the extent of intron retention and is frequently observed in known tumor suppressor genes. For missense mutations, we observed that mutations frequently subject to AI are enriched to genes related to cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T transversions. Our results suggest that mutations in known cancer-related genes and their transcripts are subjected to different levels of transcriptional or posttranscriptional regulation compared to wildtype alleles and may add an additional regulatory layer to the functions of cancer-relevant genes.