Purpose To determine whether time-dependent deep learning models can outperform single time point models in predicting preoperative upgrade of ductal carcinoma in situ (DCIS) to invasive malignancy at dynamic contrast-enhanced (DCE) breast MRI without a lesion segmentation prerequisite. Materials and Methods In this exploratory study, 154 cases of biopsy-proven DCIS (25 upgraded at surgery and 129 not upgraded) were selected consecutively from a retrospective cohort of preoperative DCE MRI in women with a mean age of 59 years at time of diagnosis from 2012 to 2022. Binary classification was implemented with convolutional neural network (CNN)-long short-term memory (LSTM) architectures benchmarked against traditional CNNs without manual segmentation of the lesions. Combinatorial performance analysis of ResNet50 versus VGG16-based models was performed with each contrast phase. Binary classification area under the receiver operating characteristic curve (AUC) was reported. Results VGG16-based models consistently provided better holdout test AUCs than did ResNet50 in CNN and CNN-LSTM studies (multiphase test AUC, 0.67 vs 0.59, respectively, for CNN models [P = .04] and 0.73 vs 0.62 for CNN-LSTM models [P = .008]). The time-dependent model (CNN-LSTM) provided a better multiphase test AUC over single time point (CNN) models (0.73 vs 0.67; P = .04). Conclusion Compared with single time point architectures, sequential deep learning algorithms using preoperative DCE MRI improved prediction of DCIS lesions upgraded to invasive malignancy without the need for lesion segmentation. Keywords: MRI, Dynamic Contrast-enhanced, Breast, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024.