Microsatellite instability, a hallmark of mismatch repair-deficient cancers, is typically associated with good response to immunotherapy. We sought to evaluate the merit of using liquid biopsies to detect microsatellite instability in subjects with stage IV colorectal adenocarcinoma.  DNA extracted from ccfDNA and buffy coats was used as source of tumor DNA and germline DNA respectively.  Aberrant microsatellite allele sizes were readily detectable in 7 of 8 cases where baseline or second treatment cycles liquid biopsy samples were available from subjects with mismatch repair-deficient cancers. The only sample that tested negative was from a subject whose primary tumor showed MSI heterogeneity and was unresponsive to immunotherapy.  MSI-H status of longitudinal liquid biopsy samples was found to correlate with response to immunotherapy.  This limited study suggests testing for microsatellite instability in liquid biopsies from subjects with advanced colorectal cancers may help in predicting response to immunotherapy.