This paper presents a two-stage methodology for anomaly detection from hyperspectral imagery that consists of transform-based feature extraction and selection, and computation of a local spatial auto-correlation statistic. First, principal component transform and 3D wavelet transform are applied to reduce redundant spectral information from hyperspectral imagery. Then feature selection based on global skewness and the portion of highly skewed sub-areas is followed to find optimal features for anomaly detection. Finally, a local indicator of spatial association (LISA) statistic is computed to account for both spectral and spatial information unlike traditional anomaly detection methodology based only on spectral information. An experiment using airborne CASI imagery is carried out to illustrate the applicability of the proposed anomaly detection methodology. From the experiments, anomaly detection based on the LISA statistic linked with the selection of optimal features outperformed both the traditional RX detector which uses only spectral information, and the case using major principal components with large eigen-values. The combination of low- and high-frequency components by 3D wavelet transform showed the best detection capability, compared with the case using optimal features selected from principal components.