Hand-held optical imaging devices are currently developed by several research groups as a noninvasive and non-ionizing method towards clinical imaging of breast cancer. The devices developed to date are typically utilized towards spectroscopic imaging via reflectance-based measurements. Additionally, a couple of devices have been used to perform 3D tomography with the addition of a second modality (e.g. ultrasound). A hand-held optical device that is unique in its ability to perform rapid 2D imaging and 3D tomography (without the use of a second modality) has been developed in our Optical Imaging laboratory. Herein, diffuse optical imaging studies are performed in breast cancer subjects. For these studies, the subject lay in a recliner chair and both breast tissues were imaged with the hand-held optical device which uses 785 nm laser source and an intensified CCD camera-based detector. Preliminary results demonstrate the ability to image invasive ductal carcinoma and lymphatic spread, as compared to the patient's medical records (e.g. xray, ultrasound, MRI). Multiple imaging studies with a subject undergoing chemotherapy demonstrated the potential to monitor response to treatment. Currently, studies are carried out to tomographically determine the 3D location of the tumor(s) in breast cancer subjects using the hand-held optical device.