Positron emission tomography (PET) is used routinely to follow therapeutic response in patients treated for non-small cell lung cancer (NSCLC). In responding patients it is generally expected that the observed decrease in fluorodeoxyglucose uptake should be similar in all lesions. In other disease entities though, isolated cases have been documented of asynchronous increases in activity in metastatic bone lesions ("bone flare") despite evidence of therapeutic response or stability in other lesions. Here, we describe four NSCLC cases in which the results of interim PET scans were misleading due to osteoblastic flare phenomenon. In all four cases, patients were treated with bevacizumab in addition to standard chemotherapy. All four patients developed isolated worsening of their skeletal metastases on PET/CT (computed tomography) analysis (increase in fluorodeoxyglucose activity) despite apparent response or stable disease elsewhere. Subsequent scans confirmed that the "worsening" was transient, consistent with a flare response. Awareness of the phenomena is important for physicians treating NSCLC patients, particularly with bevacizumab.