In recent years, multi-pixel photon counters (MPPCs) have been actively studied for use in a module for such next-generation PET systems as MRI-PET, DoI-PET, and ToF-PET scanners. In particular, Time of Flight (ToF) measurement is a challenging approach to identify the position of a γ-ray source, according to differences in the arrival times of annihilation γ rays after positron decay. Several simulations suggest a substantial improvement in the signal-to-noise ratio of PET images when using ToF information. However, ToF-PET performance is determined by the time resolution of a γ-ray sensor (including scintillators, photo-sensors and readout electronics) as a whole, thus making it often difficult to achieve ToF resolution as good as 500 ps (FWHM) in actual PET systems. This paper describes our development of a new method of ToF measurement using MPPC-based scintillation detectors. We showed that our method effectively reduces the contamination of dark noise, and minimizes the effects of time walk and timing jitter. The best ToF resolution of 213 ps (FWHM) was achieved by coupling 3×3×10 mm3 Ce:LYSO crystal with a 3×3 mm2 pixel detector. We conclude by commenting on our ultra-fast ASIC for 16-ch MPPC readout as pertaining to future applications in MPPC-PET scanners with ToF measurement capability.