We report a fall 2010 cluster of pandemic influenza A/H1N1 (pH1N1) infections in pet ferrets in Lehigh Valley region of Pennsylvania. The ferrets were associated with one pet shop. The influenza cluster occurred during a period when the existing human surveillance systems had identified little to no pH1N1 in humans in the Lehigh Valley, and there were no routine influenza surveillance systems for exotic pets. The index case was a 2.5-month-old neutered male ferret that was presented to a veterinary clinic with severe influenza-like illness (ILI). In response to laboratory notification of a positive influenza test result, and upon request from the Pennsylvania Department of Health (PADOH), the Pennsylvania Department of Agriculture (PDA) conducted an investigation to identify other ill ferrets and to identify the source and extent of infection. PDA notified the PADOH of the pH1N1 infection in the ferrets, leading to enhanced human surveillance and the detection of pH1N1 human infections in the surrounding community. Five additional ferrets with ILI linked to the pet shop were identified. This simultaneous outbreak of ferret and human pH1N1 demonstrates the important link between animal health and public health and highlights the potential use of veterinary clinics for sentinel surveillance of diseases shared between animals and humans.