Human cancers, particularly those arising in epithelial tissues, are deeply influenced by inflammation. The impact of chronic or non-resolving inflammation on tumorigenesis has been extensively studied and targeted for therapeutic benefit. However, surprisingly little is known about how acute inflammatory experiences predispose epithelial stem cells or the tissue microenvironment to tumor progression and metastasis. Acute inflammatory stressors can induce lasting changes in the chromatin and transcriptional landscape, persisting long after resolution. This process, known as “inflammatory memory,” alters the tissue’s responsiveness to subsequent stimuli, promoting either adaptive (e.g., regenerative) or maladaptive (e.g., cancerous) responses. Inflammatory memory is not exclusive to the immune system but can also be exhibited by other long-lived cells within the tissue. Thus, our lab is focused on expanding our understanding of how inflammatory experiences contribute to cancer and the metastatic niche, ultimately defining a new concept of “tissue memory and plasticity” in cancer biology.