Tumor-infiltrating B cells have emerged in recent years as key markers of patient prognosis and responsiveness to immunotherapy. Recent technical advances, such as single-cell RNA sequencing and B cell receptor immune profiling, revealed diverse subsets and the immunoglobulin landscape of B cells located within human tumors. Secreted antibodies in solid tumors exhibit multiple effector functions, with the potential to significantly impact distinct immune responses, clinical outcomes, and patient survival. Nonetheless, a few studies examine the tumor reactivity and specificity of these immunoglobulins. Here we describe our current methodology for retrieving single B cells from human primary solid tumors for single-cell RNA sequencing followed by computational analysis to identify B cell subpopulations and immunoglobulin receptor repertoires. Furthermore, we provide a technique for evaluating and quantifying the tumor-binding capabilities of expressed antibodies. This approach holds promise for future immunotherapies and enhances our understanding of their potential clinical applications.