Capitalizing on cellular homing to cancer is a promising strategy for targeting malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2 neural progenitor cells (NPC) demonstrate a tropism for cell line‐derived tumors, but their affinity for patient‐derived tumors is unknown. We tested the hypothesis that NPC accumulate in patient‐derived tumors at levels detectable by optical imaging. Mice bearing solid tumors after transplantation with patient‐derived leukemia cells and untransplanted controls received 106 fluorescent DiR‐labeled NPC daily for 1–4 days, were imaged, then sacrificed. Tissues were analyzed by immunofluorescence and flow cytometry to detect tumor cell engraftment (CD45) and NPC (FITC‐β galactosidase or DiR). Tumors consisted primarily of CD45‐positive cells and demonstrated mild fluorescence, corresponding to frequent clusters of FITC‐β gal‐positive cells. Both transplanted and control mice demonstrated the highest fluorescent signal in the spleens and other tissues of the reticuloendothelial activating system. However, only rare FITC‐β gal‐positive cells were detected in the mildly engrafted transplanted spleens and none in the control spleens, suggesting that their high DiR signal reflects the sequestration of DiR‐positive debris. The mildly engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC‐β gal‐positive cells whereas control kidneys were negative. Results indicate that NPC accumulate in tissues containing patient‐derived tumor cells in a manner that is detectable by ex vivo optical imaging and proportional to the level of tumor engraftment, suggesting a capacity to home to micrometastatic disease. As such, NPC could have significant clinical applications for the targeted diagnosis and treatment of cancer. Copyright © 2012 John Wiley & Sons, Ltd.