The advent of extensive genomic and epigenetic studies have shown that different cancer cell subpopulations are present in any given patient, each with its own unique response to therapies. Therefore, targeted therapy that only inhibits one subpopulation of cancer cells without eliminating other non-responsive sub-populations are bound to lead to relapse even though patients may show early clinical remission. Focusing on breast and liver cancers, we plan to use novel single-cell analysis and molecular beacon to identify tumor heterogeneity in order to inform patient-specific treatment plans. At the end of this project, we expect to have a positive impact by changing the paradigm for cancer classification and treatment and potentially provide new strategy to attempt to “cure” advanced breast or liver cancer. Specifically, (1) classification of advanced breast cancers or liver cancers with multiple lesions should no longer be based on subtypes or one molecular target, but rather based on the intra-tumoral heterogeneity of each tumor, which requires very different treatment options; (2) the inter-tumoral heterogeneity of primary and metastatic tumors (or multiple lesions) requires different drug combinations; and (3) the inter-tumoral heterogeneity from each individual patient also requires individualized combination of drug therapy. We envision that once we have established the database for this information, it will be feasible to rapidly translate to clinical trials where individualized combinations of therapies can be tailored to eliminate each sub-population of cancer cell heterogeneity and potentially “cure” cancer in the patients with breast or liver cancer.