The main difference between Personally Identifiable Information (PII) and Protected Health Information (PHI) lies in their scope and context. PII refers to any information that can be traced to an individual's identity, such as name, Social Security number, address, email address, and biometric data. On the other hand, PHI is a subset of PII and specifically pertains to health information shared with HIPAA-covered entities, encompassing 18 specific identifiers. While PII is a broader term covering various types of identifiable information, PHI is more specific and is associated with healthcare and HIPAA regulations.