2017 IEEE.Efficient Human Epithelial-2 cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper proposes an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. In addition to describing the proposed classification framework, this paper elaborates several interesting observations and findings obtained by our investigation. They include the important factors that impact network design and training, the role of rotation-based data augmentation for cell images, the effectiveness of cell image masks for classification, and the adaptability of the CNN-based classification system across different datasets. Extensive experimental study is conducted to verify the above findings and compares the proposed framework with the well-established image classification models in the literature. The results on benchmark datasets demonstrate that 1) the proposed framework can effectively outperform existing models by properly applying data augmentation, 2) our CNN-based framework has excellent adaptability across different datasets, which is highly desirable for cell image classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014.