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Colorectal cancer (CRC) is the third most common malignancy and the second most common deadly cancer worldwide as of 2020. Unusual presentation of this cancer with locally advanced disease is rare and seen in only 5% to 22% of cases. We present the case of a 53-year-old male who had invasive cecal adenocarcinoma with phlegmon of the abdominal wall musculature at presentation and an aggressive course that did not respond to the standard lines of therapy. In the current era of ongoing tremendous developments in colorectal cancer diagnosis and treatment, this uncommon case reminds us that locally advanced CRC is still a challenge to manage. Precision medicine with treatment strategies tailored to an individual’s genetic, environmental and lifestyle factors is the current need.