An intraoperative registration and tracking system includes an optical source configured to illuminate tissue intraoperatively with electromagnetic radiation at a substantially localized spot so as to provide a photoacoustic source at the substantially localize spot, an optical imaging system configured to form an optical image of at least a portion of the tissue and to detect and determine a position of the substantially localized spot in the optical image, an ultrasound imaging system configured to form an ultrasound image of at least a portion of the tissue and to detect and determine a position of the substantially localized spot in the ultrasound image, and a registration system configured to determine a coordinate transformation that registers the optical image with the ultrasound image based at least partially on a correspondence of the spot in the optical image with the spot in the ultrasound image.