Ipsilateral breast tumor recurrence (IBTR) occurred in 42 of 488 (9%) pathologically evaluable patients enrolled in NSABP protocol B-06 with a mean potential follow-up of 103 months (range 68-161 months) following treatment for Stage I and II invasive breast cancer by lumpectomy and local breast irradiation (LXRT). IBTR were observed at or close to the same quadrant as the index cancers and their histologic types and nuclear grades were similar if not identical in 95 and 93%, respectively. This information confirms our earlier findings which indicated that multicentricity is of little or no clinical significance in the treatment of breast cancer by LXRT; breast cancers rarely if ever change their biologic potential once clinically detected; and lastly, most if not all IBTR represent residual cancer. Cox regression analyses revealed only a patient age less than 35 years to be significantly related to IBTR. No relationship between IBTR and so-called extensive intraductal component (EIC) or 31 other pathologic features of the index cancers was found. Overall survival was significantly related to nodal status (P = 0.01), nuclear grade (P = less than 0.001) histologic tumor type (P = 0.01) and IBTR (P = less than 0.001). This latter was considered as an indicator rather than instigator of distant disease and reduced survival since the latter is no different in patients treated by LXRT, lumpectomy alone after which IBTR is much more frequent, or mastectomy, which precludes its expression. We conclude that there are as yet no viable markers which would contraindicate treating patients with breast cancer by LXRT.