We describe what is, to the best of our knowledge, the first pilot study of coregistered tomographic x-ray and optical breast imaging. The purpose of this pilot study is to develop both hardware and data processing algorithms for a multimodality imaging method that provides information that neither x-ray nor diffuse optical tomography (DOT) can provide alone. We present in detail the instrumentation and algorithms developed for this multimodality imaging. We also present results from our initial pilot clinical tests. These results demonstrate that strictly coregistered x-ray and optical images enable a detailed comparison of the two images. This comparison will ultimately lead to a better understanding of the relationship between the functional contrast afforded by optical imaging and the structural contrast provided by x-ray imaging. © 2005 Society of Photo-Optical Instrumentation Engineers.