Abstract Multi-instance learning (MIL) deals with the tasks where each example is represented by a bag of instances. A bag is positive if it contains at least one positive instance, and negative otherwise. The positive instances are also called key instances. Only bag labels are observed, whereas specific instance labels are not available in MIL. Previous studies typically assume that training and test data follow the same distribution, which may be violated in many real-world tasks. In this paper, we address the problem that the distribution of key instances varies between training and test phase. We refer to this problem as MIL with key instance shift and solve it by proposing an embedding based method MIKI. Specifically, to transform the bags into informative vectors, we propose a weighted multi-class model to select the instances with high positiveness as instance prototypes. Then we learn the importance weights for transformed bag vectors and incorporate original instance weights into them to narrow the gap between training/test distributions. Experimental results validate the effectiveness of our approach when key instance shift occurs.