Analyzing colon biopsies is becoming time consuming and a financial burden as colonoscopy is now the main screening and diagnostic procedure of the main gastrointestinal diseases. Colon sampling can provide important information when used accordingly; otherwise it may only load the medical system unnecessarily. Our aim was to retrospectively analyze criteria for colon biopsies and correlate the diagnostic value of randomly sampling colon, especially in patients with diarrhea. This was a retrospective study on 2109 colonoscopies done over one year. Data was collected from the ENDORAD system and included variables such as: age, gender, quality of preparation, procedure, symptoms, biopsies (type, location), and endoscopy and histology findings. Data was analyzed in a descriptive manner. Out of 496 random biopsies, only 7.4% had positive histology findings. The main symptom was diarrhea and 186 cases of patients complaining of diarrhea with normal colonoscopy had random colon sampling. In 5.3% of these cases histology assessment showed changes of microscopic colitis. Fisher’s test was significant when correlating the odds of having random biopsies in patients with and without diarrhea and patients younger and older than 60. Random sampling of colon during colonoscopies should be done only in selected patients otherwise it has a low diagnostic value.