X-ray mammography, the current gold standard for breast cancer detection, has a 20% false-negative rate (cancer is undetected) and increases in younger women with denser breast tissue. Diffuse optical imaging (DOI) is a safe (nonionizing), and relatively inexpensive method for noninvasive imaging of breast cancer in human subjects (including dense breast tissues) by providing physiological information (e.g. oxy- and deoxy- hemoglobin concentration). At the Optical Imaging Laboratory, a hand-held optical imager has been developed which employs a breast contourable probe head to perform simultaneous illumination and detection of large surfaces towards near real-time imaging of human breast cancer. Gen-1 and gen-2 versions of the handheld optical imager have been developed and previously demonstrated imaging in tissue phantoms and healthy human subjects. Herein, the hand-held optical imagers are applied towards in vivo imaging of breast cancer subjects in an attempt to determine the ability of the imager to detect breast tumors. Five female human subjects (ages 51-74) diagnosed with breast cancer were imaged with the gen-1 optical imager prior to surgical intervention. One of the subjects was also imaged with the gen-2 optical imager. Both imagers use 785 nm laser diode sources and ICCD camera detectors to generate 2D surfaces maps of total hemoglobin absorption. The subjects lay in supine position and images were collected at various locations on both the ipsilateral (tumor-containing) and contralateral (non-tumor containing) breasts. The optical images (2D surface maps of optical absorption due to total hemoglobin concentration) show regions of higher intensity at the tumor location, which is indicative of increased vasculature and higher blood content due to the presence of the tumor. Additionally, a preliminary result indicates the potential to image lymphatic spread. This study demonstrates the potential of the hand-held optical devices to noninvasively image breast cancer in human subjects.