Vitamin D deficiency has been previously reported to be a risk factor for breast cancer progression, though whether this association represents a causal relationship is not known. In this report, human breast cancer cells are found to proliferate faster in the bone of nude mice deficient in vitamin D compared with those in vitamin D–sufficient mice. Vitamin D deficiency, predominantly through induction of increased bone resorption by osteoclasts (here highlighted by red staining for tartrate-resistant acid phosphatase activity), modifies the microenvironment of bone to enhance early breast cancer cell proliferation. For details, see the article by Ooi and colleagues on page 1835 of this issue.