Recently, there have been significant progress in digital cytology, whole-slide imaging, and Artificial Intelligence (AI). Artificial intelligence (AI) can help to make a mathematical model that can extract actionable clinical information regarding disease identification, stratification and management. The “computational cytology” is an emerging field that encompasses the digital cytology, patient’s metadata and artificial intelligence. By definition, it refers to the incorporation of digital imaging data from the cytology smear, patient metadata and molecular data into a mathematical model using a computer to obtain clinically useful information. In the present chapter, the development of computational cytology and its potential applications in cytology are discussed.