The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained. Additionally, the application of an ultrasound gel to the imaging surface may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate imaging of tissues and cells with high resolution and contrast. We have recently developed a novel method for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells using MPM. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders.