RUNX family proteins are expressed from alternate promoters, giving rise to different N-terminal forms, but the functional difference of these isoforms is not understood. Here, we show that growth of a human B lymphoblastoid cell line infected with Epstein-Barr virus is inhibited by RUNX1c but not by RUNX1b. This gives a novel functional assay for the unique N-terminus of RUNX1c, and amino acids of RUNX1c required for the effect have been identified. Primary resting B cells contain RUNX1c, consistent with the growth inhibitory effect in B cells. The oncogene TEL-RUNX1 lacks the N-terminus of RUNX1c because of the TEL fusion and does not inhibit B cell growth. Mouse Runx1c lacks some of the sequences required for human RUNX1c to inhibit B cell growth, indicating that this aspect of human B cell growth control may differ in mice. Remarkably, a cell-penetrating peptide containing the N-terminal sequence of RUNX1c specifically antagonizes the growth inhibitory effect in B lymphoblastoid cells and might be used to modulate the function of human RUNX1c.