Abstract Background Pre-existing chronic conditions can influence cancer diagnosis and outcomes. The study aimed to examine variations in diagnostic pathways and outcomes in colorectal cancer (CRC) patients by comorbidity status and socio-demographic characteristics in the provinces of Milan and Lodi, Northern Italy. Methods A population-based cohort study using linked administrative health data from the Agency for Health Protection (ATS) of Milan was conducted on individuals aged ≥18 years diagnosed with CRC in 2014-2017. We examined pathways to cancer diagnosis, stage at diagnosis and short-term mortality by specific comorbidities and sociodemographic factors. Results Among the 5,272 colon cancer and 2,120 rectal cancer patients, 43.9% and 61.5%, respectively, had at least one pre-existing comorbidity, most frequently hypertension (52.7% and 49.9%) and cardiovascular disease (CVD, 23.2% and 18.5%). Cancer diagnostic pathways included screening (4.1% colon and 4.4% rectal cancer patients), EP (22.8% and 12.6%) and inpatient/outpatient admission (73.1% and 82.9%). At multivariable logistic regression, patients with pre-existing cerebrovascular or neurological diseases had significantly higher odds of EP for CRC. In the multinomial logistic regression analysis, the odds of EP were significantly higher for patients aged <50 or ≥ 80 (vs 60-69), belonging to the highest deprivation group and being widowed (vs married). The odds of screen-detected CRC were lower for patients with multimorbidity (2 vs 0 comorbidities: adjusted OR = 0.32, 95% CI 0.14-0.75). 30-day and one-year mortality were higher in colon cancer patients with EP vs inpatient/outpatient (aOR=2.46, 95%CI 1.95-3.09; aOR=2.02, 95%CI 1.74-2.35 respectively). As the number of chronic conditions increased, mortality increased especially at one year. One-year mortality was also higher for rectal cancer patients with 3+ comorbidities (vs no comorbidities). Key messages • Patients with pre-existing chronic conditions had a lower likelihood of screening, higher odds of emergency CRC diagnosis and higher mortality. EPs occur in one in five CRC patients. • Tailored interventions might be needed to facilitate CRC screening, reducing emergency diagnoses and improving health outcomes for the large number of patients with chronic conditions.