The goal of the proposed research is to translate single-cell label-free photoacoustic microscopy (PAM) into clinical practice. In vivo PAM has been invented for early-cancer detection and functional, metabolic, or molecular imaging by physically integrating optical and ultrasonic waves. Unlike ionizing x-ray radiation, light poses n health hazard and reveals molecular contrasts. Unfortunately, light does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution optical imaging-such as confocal microscopy, two-photon microscopy, and optical coherence tomography-has been restricted to tissue depths within the optical diffusion limit (~1 mm in the skin). PAM breaks through this limitation by taking advantage of the fact that ultrasonic scattering per unit path-length in tissue is ~1000 times less than optical scattering. It is exquisitely sensitive to optica absorption contrasts, enabling it to image far more molecules than fluorescence microscopy. PAM may hold the key to the earliest detection of cancer by in vivo label-free quantification of hyper-metabolism, the quintessential hallmark of cancer. The proposed immediate clinical translation of this technology will enable in vivo imaging and detection of single circulating cell, especially circulating tumor cells for cancer screening, detection, prognosis, and monitoring. We propose the following specific aims to clinically translate PAM. Aim 1. High-resolution label-free PAM for in vivo imaging of circulating single red blood and tumor cells. Aim 2. High-throughput label-free PAM for in vivo imaging of single circulating tumor cells (CTCs).