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Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3 + and CD8 + TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3 + ( P = 0.0136), CD8 + ( P = 0.0092), and CD25 + ( P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.