The rapid digitization of histopathology slides has opened new opportunities for computational tools in clinical and research workflows. Content-based slide retrieval can help pathologists identify morphologically and semantically related precedent cases, supporting expert diagnosis and example-based education. Effective retrieval of whole-slide images (WSIs), however, remains challenging because gigapixel slides contain abundant irrelevant content, focal diagnostic patterns and slide-level semantic information that must be represented at a practicable search cost. Here we present PathSearch, a retrieval framework that combines fine-grained attentive mosaics with slide-level embeddings aligned through vision-language contrastive learning. Trained on 6,926 slide-report pairs, PathSearch captures both fine-grained morphological cues and high-level semantic patterns to enable accurate and flexible retrieval. The framework supports two key functionalities: (1) mosaic-based image-to-image (I2I) retrieval, ensuring accurate and efficient slide search; and (2) multimodal retrieval, where text queries can directly retrieve relevant slides. PathSearch was evaluated on eight tasks comprising 5,021 evaluation slides, spanning malignancy assessment on frozen and hematoxylin and eosin (H\&E)-stained slides, lymph-node metastasis detection, tumor subtyping, mixed-gallery rare-cancer retrieval, and hepatocellular carcinoma (HCC) risk stratification. Internal and external experimental results demonstrate that PathSearch consistently outperforms the strongest existing methods without compromising multimodal accuracy. A multi-center reader study further demonstrated increases in task-level mean diagnostic accuracy, confidence, and inter-observer agreement with PathSearch's support. Together, these results support the effectiveness of PathSearch across diverse retrieval tasks and evaluation settings.

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