As we have previously shown that osteopontin (OPN) is a downstream target of Tcf-4 in a rat breast epithelial cell line Rama37 (El-Tanani et al, 2001a), the aim of the present study was to investigate how the Tcf-4/OPN link is regulated in human breast cancer and modulates human breast cancer progression. The gene discussed is SPP1; the disease is breast cancer.