The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung's disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.