The article by Vergallo et al1 in this issue of JAMA Cardiology supports a hypothesis that healed plaques are a marker for reduced acute coronary syndrome (ACS) risk. This commentary expands on this idea by examining a mechanistic hypothesis of their results beyond looking at healing just as a marker. Specifically, failed healing, which correlated in the study by Vergallo et al1 with long core axial extent, predisposes plaque ruptures to progress to ACS. Acute coronary syndrome may require a double hit of both rupture and impaired healing. This is somewhat analogous to the situation in oncology, where after studying oncogenes for decades, it was discovered that 50% of all human cancers also have a mutation in the p53 tumor suppressor gene.