Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen expressed on multiple tumors and has no significant expression on normal human tissues. ROR1 is highly upregulated in chronic lymphocytic leukemia (CLL) B cells. NOD-scid IL2rg (NSG) mice engrafted with human CD34 hematopoietic progenitor cells (huNSG) achieved multilineage human immune cell reconstitution including B cells， T cells， NK cells， and DCs. Like the CLL patients， huNSG mice have abnormally high percentage of CD5-expressing B cells in the periphery. In light of this， we aim to determine whether ROR1 is expressed on huNSG B cells. Using flow cytometry analysis， we found that ROR1 was highly expressed in a proportion of bone marrow， spleen， and blood B cells， which were mostly immature B cells. Transplantation of the oncogene TCL-1-transduced CD34 cells in neonatal NSG mice did not increase the frequency of ROR1-expressing B cells， but the mouse with the highest engraftment of transduced cells developed a tumor-like lump consisting of a high percentage of ROR1-expressing B cells. This study highlights the potential use of huNSG mice to study B cell malignant diseases and to evaluate immunotherapeutics targeting ROR1.