With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples are not fit for tissue-based CGP tests, a blood-based CGP test (liquid biopsy) is available as an alternative option. Three CGP tests, “OncoGuide NCCTMOncopanel System (124 genes)”, “FoundationOne®CDx (324 genes)”, and “Founda-tionOne®CDx Liquid (324 genes)”, are now reimbursed by public insurance in 233 hospitals designated for cancer genomic medicine in Japan. In biliary tract cancer, the prevalence of druggable variants is relatively higher compared to other cancer types and the European Society for Medical Oncology recommends routine use of CGP tests for advanced biliary tract cancer to guide treatment options. The latest National Cancer Center Network guideline lists eight druggable markers (NTRK fusion, MSI-H, TMB-H, BRAF V600E, FGFR2 fusions/rearrangement, IDH1 mutations, RET fusion, and HER2 overexpression) and matched therapies. In Japan, matched therapies for four markers (NTRK, MSI-H, TMB-H, and FGFR2) are reimbursed by public insurance (as of September 2022). The progress of genomic profiling technology will contribute to the improvement of the dismal clinical outcomes of this disease in the future.